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THU0299 B Cell Compartment and Pharmacodynamics of Belimumab in Systemic Lupus Erythematosus: Early Clinical Efficacy by Depletion of CD27- and Increase of CD27+ B Cells
  1. L. Quartuccio1,
  2. G. De Marchi1,
  3. F.M. Rossi2,
  4. F. Zuliani1,
  5. M. Bond1,
  6. L. Picco1,
  7. P. Masolini1,
  8. F. Rizzolio3,
  9. S. De Vita1
  1. 1Department of Biological and Medical Sciences, Rheumatology Clinic, University Hospital of Udine, Udine
  2. 2Centro di Riferimento Oncologico (CRO), Clinical and Experimental Onco-Hematology Unit
  3. 3Centro di Riferimento Oncologico (CRO), Experimental and Clinical Pharmacology Unit, Aviano (PN), Italy

Abstract

Background Belimumab, a human anti-BAFF monoclonal antibody that inhibits soluble BAFF, is effective in systemic lupus erythematosus (SLE), and leads to a partial B cell depletion. However, which subset of B cells may be the main therapeutic target of belimumab in SLE is still unclear.

Objectives Primary objective of this study was to evaluate the effect of belimumab on the expression of BAFF receptor (BAFFR) on B cells through 12 months of belimumab treatment in SLE, and to correlate BAFFR expression with changes in B cell subsets.

Methods Twelve consecutive patients with SLE (all female, age 44±7,8 yrs, 12,6±5,4 yrs of disease duration) undergoing belimumab therapy were studied. All patients received at least two immunosuppressors before belimumab. All patients were taking glucocorticoids at baseline [median (range): 7,5 (0–40) mg/day of prednisone or equivalent)], and 11/12 also at least one immunosuppressor. Median SLEDAI-2k score at baseline was 8,5 (range 8–15). Samples were collected and analysed at baseline (T0), month +3 (T3), +6 (T6), +9 (T9) and +12 (T12) for clinical and biological parameters. B cells subsets were characterized by multiparametric flowcytometry on a BD FACSCanto flowcytometer. The expression of BAFFR was also analysed as Mean Fluorescence Intensity (MFI). Parametric or non-parametric tests were used, as appropriate based on variable distribution. Data is reported as mean±standard error.

Results A transient statistically significant increase of BAFFR MFI was observed from T0 to T3 (p=0,004) and from T0 to T6 (p=0,066) with a subsequent decrease until T12 (table 1). Interestingly, this course was similar to that observed in CD19+CD27+ cell subset (table 1), that showed a transient significant increase at T3 (p=0,014) and T6 (p=0,025) in 9/12 patients, with a subsequent slightly significant decrease from T6 to T12 (p=0,05) in all patients. Globally, a decrease of CD19+ cells was observed from T0 to T12 (p=0,19, table 1). This course is consistent with that observed in the CD27- B cell subset, that showed a decrease from T0 to T3 (p=0,14) and from T0 to T6 (p=0,14), and the decrease was persistent from T6 to T12 (p=0,6). SLEDAI-2k score decreased from T0 to T3 (p=0,007), to T6 (p=0,003) and to T12 (p=0,03) (table 1).

Table 1

Conclusions BAFF depletion differently acts on B cell subsets, CD19+27+ subset being able to increase BAFFR and transiently expand themselves, while CD19+27- being more sensitive to BAFF deprivation, and faster decreasing. Thus, early clinical response may be related to the changes in the CD27+/CD27- B cell ratio.

Disclosure of Interest None declared

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